A number of factors call for research on the impact of aging on learning and memory, especially age-related memory disorders such as Alzheimer's disease. A major difficulty in this area is the lack of a specific knowledge of the neural basis of normal learning. It is likely that the specification of the neural basis of learning and its disorders will require the use of animal models that permit invasive treatments and short-duration life span experimentation. Classical conditioning of the rabbit nictitating membrane (NM) response has become the most utilized and productive model system for neurobiological studies of associative learning in mammals. A growing "system map" that specifies the sites of neural involvement in NM conditioning has been developed over the last 10 years, and can now be used for precise comparisons of the sites and patterns of learning-related neuronal activity in young and aged animals. in addition, direct manipulation of brain systems known to be involved in NM conditioning can be used in young animals to model age-related impairments and to prevent deficits in older animals. Such findings have broad implications for our understanding of the neural bases of memory impairments, and may suggest methods for preventing or treating geriatric memory and learning disorders. The specific aims of the project are (1) to examine the impact of aging on behavioral learning and on the patterns of conditioned neural activity in the hippocampus and septal region, using NM conditioning to the New Zealand White rabbit; (2) to assess the viability of cholinergic impairments in young and midaged rabbits as a model of functional deficits that appear in aged subjects; and (3) to determine if electrical stimulation that optimizes the patterns of septohippocampal learning dependent neural activity in young animals can ameliorate age-related behavioral impairments.